tbuckley/cabot-search huggingface dataset:
Burden of Long-Term Morbidity Borne by Survivors of Acute Myeloid Leukemia Treated With Blood or Marrow Transplantation: The Results of the BMT Survivor Study
Authors: Saro H. Armenian, Yanjun Chen, Lindsay Hageman, Jessica Wu, Wendy Landier, Alysia Bosworth, Liton Francisco, Elizabeth Schlichting, Ravi Bhatia, Donna Salzman, F. Lennie Wong, Daniel J. Weisdorf, Stephen J. Forman, Mukta Arora, Smita Bhatia
Journal: Journal of Clinical Oncology (2022)

Blood or marrow transplantation (BMT) is an integral part of consolidation and/or salvage therapy for patients with acute myeloid leukemia (AML). With the growing population of AML survivors, there is a need to understand the quality of their survival.
Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors
Authors: Andrew B. Lassman, Khê Hoang-Xuan, Mei-Yin C. Polley, Alba A. Brandes, J. Gregory Cairncross, Johan M. Kros, Lynn S. Ashby, Martin J.B. Taphoorn, Luis Souhami, Winand N.M. Dinjens, Nadia N. Laack, Mathilde C.M. Kouwenhoven, Karen L. Fink, Pim J. French, David R. Macdonald, Denis Lacombe, Minhee Won, Thierry Gorlia, Minesh P. Mehta, Martin J. van den Bent
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the basis of the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization for the Research and Treatment of Cancer 26951 and Radiation Therapy Oncology Group 9402 phase III trials initiated in 1990s, which both studied radiotherapy with/without neo/adjuvant procarbazine, lomustine, and vincristine (PCV) for newly diagnosed anaplastic oligodendroglial tumors. The median follow-up duration in both was 18-19 years. For European Organization for the Research and Treatment of Cancer 26951, median, 14-year, and probable 20-year overall survival rates without versus with PCV were 2.6 years, 13.4%, and 10.1% versus 3.5 years, 25.1%, and 16.8% (N = 368 overall; hazard ratio [HR] 0.78; 95% CI, 0.63 to 0.98; P = .033), with 1p19q codeletion 9.3 years, 26.2%, and 13.6% versus 14.2 years, 51.0%, and 37.1% (n = 80; HR 0.60; 95% CI, 0.35 to 1.03; P = .063), respectively. For Radiation Therapy Oncology Group 9402, analogous results were 4.8 years, 16.5%, and 11.2% versus 4.8 years, 29.1%, and 24.6% (N = 289 overall; HR 0.79; 95% CI, 0.61 to 1.03; P = .08), with codeletion 7.3 years, 25.0%, and 14.9% versus 13.2 years, 46.1%, and 37% (n = 125; HR 0.61; 95% CI, 0.40 to 0.94; P = .02), respectively. With that, the studies show similar long-term survival even without tumor recurrence in a significant proportion of patients after first-line treatment with radiotherapy/PCV.
Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts
Authors: Benjamin P. Sharpe, Annette Hayden, Antigoni Manousopoulou, Andrew Cowie, Robert C. Walker, Jack Harrington, Fereshteh Izadi, Stella P. Breininger, Jane Gibson, Oliver Pickering, Eleanor Jaynes, Ewan Kyle, John H. Saunders, Simon L. Parsons, Alison A. Ritchie, Philip A. Clarke, Pamela Collier, Nigel P. Mongan, David O. Bates, Kiren Yacqub-Usman, Spiros D. Garbis, Zoë Walters, Matthew Rose-Zerilli, Anna M. Grabowska, Timothy J. Underwood
Journal: Cell Reports Medicine (2022)
The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19
Authors: Christoph Schultheiß, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Svenja-Sibylla Henkes, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Höll, Michael Gekle, Rafael Mikolajczyk, Mascha Binder
Journal: Cell Reports Medicine (2022)
Simplexviruses Successfully Adapt to Their Host by Fine-Tuning Immune Responses
Authors: Alessandra Mozzi, Rachele Cagliani, Chiara Pontremoli, Diego Forni, Irma Saulle, Marina Saresella, Uberto Pozzoli, Gioia Cappelletti, Chiara Vantaggiato, Mario Clerici, Mara Biasin, Manuela Sironi
Journal: Molecular Biology and Evolution (2022)

Abstract Primate herpes simplex viruses are species-specific and relatively harmless to their natural hosts. However, cross-species transmission is often associated with severe disease, as exemplified by the virulence of macacine herpesvirus 1 (B virus) in humans. We performed a genome-wide scan for signals of adaptation of simplexviruses to their hominin hosts. Among core genes, we found evidence of episodic positive selection in three glycoproteins, with several selected sites located in antigenic determinants. Positively selected noncore genes were found to be involved in different immune-escape mechanisms. The herpes simplex virus (HSV)-1/HSV-2 encoded product (ICP47) of one of these genes is known to down-modulate major histocompatibility complex class I expression. This feature is not shared with B virus, which instead up-regulates Human Leukocyte Antigen (HLA)-G, an immunomodulatory molecule. By in vitro expression of different ICP47 mutants, we functionally characterized the selection signals. Results indicated that the selected sites do not represent the sole determinants of binding to the transporter associated with antigen processing (TAP). Conversely, the amino acid status at these sites was sufficient to determine HLA-G up-regulation. In fact, both HSV-1 and HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. These differences might contribute to the severity of B virus infection in humans. Importantly, they indicate that the evolution of ICP47 in HSV-1/HSV-2 led to the loss of an immunosuppressive effect. Thus, related simplexviruses finely tune the balance between immunosuppressive and immunostimulatory pathways to promote successful co-existence with their primate hosts.
Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Authors: Xinbo Wang, Jiaying Miao, Sizhen Wang, Rongxi Shen, Shuo Zhang, Yurao Tian, Min Li, Daojun Zhu, Anlong Yao, Wei Bao, Qun Zhang, Xingming Tang, Xingyun Wang, Jieshou Li
Journal: Molecular Cancer (2022)

Abstract Background Undifferentiated carcinoma with osteoclast-like giant cells (OGCs) of pancreas (UCOGCP) is a rare subtype of pancreatic ductal adenocarcinoma (PDAC), which had poorly described histopathological and clinical features. Methods In this study, single-cell RNA sequencing (scRNA-seq) was used to profile the distinct tumor microenvironment of UCOGCP using samples obtained from one UCOGCP patient and three PDAC patients. Bioinformatic analysis was carried out and immunohistochemical (IHC) staining was used to support the findings of bioinformatic analysis. After quality control of the raw data, a total of 18,376 cells were obtained from these four samples for subsequent analysis. These cells were divided into ten main cell types following the Seurat analysis pipeline. Among them, the UCOGCP sample displayed distinct distribution patterns from the rest samples in the epithelial cell, myeloid cell, fibroblast, and endothelial cell clusters. Further analysis supported that the OGCs were generated from stem-cell-like mesenchymal epithelial cells (SMECs). Results Functional analysis showed that the OGCs cluster was enriched in antigen presentation, immune response, and stem cell differentiation. Gene markers such as LOX, SPERINE1, CD44, and TGFBI were highly expressed in this SMECs cluster which signified poor prognosis. Interestingly, in myeloid cell, fibroblasts, and endothelial cell clusters, UCOGCP contained higher percentage of these cells and unique subclusters, compared with the rest of PDAC samples. Conclusions Analysis of cell communication depicted that CD74 plays important roles in the formation of the microenvironment of UCOGCP. Our findings illustrated the genesis and function of OGCs, and the tumor microenvironment (TME) of UCOGCP, providing insights for prognosis and treatment strategy for this rare type of pancreatic cancer.
B cell targeting in CAR T cell therapy: Side effect or driver of CAR T cell function?
Authors: Gregory M. Chen, Jan Joseph Melenhorst, Kai Tan
Journal: Science Translational Medicine (2022)

Chimeric antigen receptor (CAR) T cell therapies targeting CD19 and CD22 have been successful for treating B cell cancers, but CAR T cells targeting non–B cell cancers remain unsuccessful. We propose that rather than being strictly a side effect of therapy, the large number of CAR interactions with normal B cells may be a key contributor to clinical CAR T cell responses.
Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi
Authors: Rhea J. Longley, Matthew J. Grigg, Kael Schoffer, Thomas Obadia, Stephanie Hyslop, Kim A. Piera, Narimane Nekkab, Ramin Mazhari, Eizo Takashima, Takafumi Tsuboi, Matthias Harbers, Kevin Tetteh, Chris Drakeley, Chetan E. Chitnis, Julie Healer, Wai-Hong Tham, Jetsumon Sattabongkot, Michael T. White, Daniel J. Cooper, Giri S. Rajahram, Bridget E. Barber, Timothy William, Nicholas M. Anstey, Ivo Mueller
Journal: Cell Reports Medicine (2022)

Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P. knowlesi, which also infects humans. P. vivax and P. knowlesi are co-endemic across much of South East Asia, making it important to design serological markers that minimize cross-reactivity in this region. To determine the degree of IgG cross-reactivity against a panel of P. vivax serological markers, we assayed samples from human patients with P. knowlesi malaria. IgG antibody reactivity is high against P. vivax proteins with high sequence identity with their P. knowlesi ortholog. IgG reactivity peaks at 7 days post-P. knowlesi infection and is short-lived, with minimal responses 1 year post-infection. We designed a panel of eight P. vivax proteins with low levels of cross-reactivity with P. knowlesi. This panel can accurately classify recent P. vivax infections while reducing misclassification of recent P. knowlesi infections.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
Authors: Joseph D. Khoury, Eric Solary, Oussama Abla, Yassmine Akkari, Rita Alaggio, Jane F. Apperley, Rafael Bejar, Emilio Berti, Lambert Busque, John K. C. Chan, Weina Chen, Xueyan Chen, Wee-Joo Chng, John K. Choi, Isabel Colmenero, Sarah E. Coupland, Nicholas C. P. Cross, Daphne De Jong, M. Tarek Elghetany, Emiko Takahashi, Jean-Francois Emile, Judith Ferry, Linda Fogelstrand, Michaela Fontenay, Ulrich Germing, Sumeet Gujral, Torsten Haferlach, Claire Harrison, Jennelle C. Hodge, Shimin Hu, Joop H. Jansen, Rashmi Kanagal-Shamanna, Hagop M. Kantarjian, Christian P. Kratz, Xiao-Qiu Li, Megan S. Lim, Keith Loeb, Sanam Loghavi, Andrea Marcogliese, Soheil Meshinchi, Phillip Michaels, Kikkeri N. Naresh, Yasodha Natkunam, Reza Nejati, German Ott, Eric Padron, Keyur P. Patel, Nikhil Patkar, Jennifer Picarsic, Uwe Platzbecker, Irene Roberts, Anna Schuh, William Sewell, Reiner Siebert, Prashant Tembhare, Jeffrey Tyner, Srdan Verstovsek, Wei Wang, Brent Wood, Wenbin Xiao, Cecilia Yeung, Andreas Hochhaus
Journal: Leukemia (2022)

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles
Authors: Van Dat Bui, Soyoung Son, Wilbin Xavier, Van Quy Nguyen, Jae Min Jung, Jungmi Lee, Sol Shin, Wooram Um, Jae Yoon An, Chan Ho Kim, Yeari Song, Yuce Li, Jae Hyung Park
Journal: Biomaterials (2022)
Allograft Rejection Surveillance In Heart Transplantation: Is There a Better Way?
Authors: James C. Fang, Omar Wever-Pinzon
Journal: Circulation (2022)

eart transplantation continues to be the definitive treatment for end-stage heart failure.Advances in immunosuppression and patient care protocols have led to improved survival after transplant, with a median that extends to nearly 15 years among first-year survivors. 1Although the incidence of allograft rejection (AR) has declined, it remains a significant cause of morbidity and mortality, particularly in younger recipients. 2 AR can lead to chronic graft injury and dysfunction, cardiac allograft vasculopathy, and mortality.
Combining the strengths of radiologists and AI for breast cancer screening: a retrospective analysis
Authors: Christian Leibig, Moritz Brehmer, Stefan Bunk, Danalyn Byng, Katja Pinker, Lale Umutlu
Journal: The Lancet Digital Health (2022)

We propose a decision-referral approach for integrating artificial intelligence (AI) into the breast-cancer screening pathway, whereby the algorithm makes predictions on the basis of its quantification of uncertainty. Algorithmic assessments with high certainty are done automatically, whereas assessments with lower certainty are referred to the radiologist. This two-part AI system can triage normal mammography exams and provide post-hoc cancer detection to maintain a high degree of sensitivity. This study aimed to evaluate the performance of this AI system on sensitivity and specificity when used either as a standalone system or within a decision-referral approach, compared with the original radiologist decision.
Inactivating Amplified HER2: Challenges, Dilemmas, and Future Directions
Authors: Mark M. Moasser
Journal: Cancer Research (2022)

The pharmaceutical inactivation of driver oncogenes has revolutionized the treatment of cancer, replacing cytotoxic chemotherapeutic approaches with kinase inhibitor therapies for many types of cancers. This approach has not yet been realized for the treatment of HER2-amplified cancers. The monotherapy activities associated with HER2-targeting antibodies and kinase inhibitors are modest, and their clinical use has been in combination with and not in replacement of cytotoxic chemotherapies. This stands in sharp contrast to achievements in the treatment of many other oncogene-driven cancers. The mechanism-based treatment hypothesis regarding the inactivation of HER2 justifies expectations far beyond what is currently realized. Overcoming this barrier requires mechanistic insights that can fuel new directions for pursuit, but scientific investigation of this treatment hypothesis, particularly with regards to trastuzumab, has been complicated by conflicting and confusing data sets, ironclad dogma, and mechanistic conclusions that have repeatedly failed to translate clinically. We are now approaching a point of convergence regarding the challenges and resiliency in this tumor driver, and I will provide here a review and opinion to inform where we currently stand with this treatment hypothesis and where the future potential lies.
Targeting Ferroptosis Vulnerability in Synovial Sarcoma: Is It All About ME1?
Authors: Vivek Subbiah, Boyi Gan
Journal: Clinical Cancer Research (2022)

Understanding metabolic dependencies and their therapeutic vulnerabilities is key to precision oncology. Malic enzyme 1 (ME1) is frequently overexpressed in cancers with protumorigenic effects. In contrast, consistent loss of ME1 expression in synovial sarcoma compared with other sarcomas indicates a unique ferroptosis liability for precision therapy in this form of cancer. See related article by Brashears et al., p. 3573.
Optimal target saturation of ligand-blocking anti-GITR antibody IBI37G5 dictates FcγR-independent GITR agonism and antitumor activity
Authors: Huisi Liu, Weiwei Wu, Gangyu Sun, Tiongsun Chia, Lei Cao, Xiaodan Liu, Jian Guan, Fenggen Fu, Ying Yao, Zhihai Wu, Shuaixiang Zhou, Jie Wang, Jia Lu, Zhihui Kuang, Min Wu, Luan He, Zhiyuan Shao, Dongdong Wu, Bingliang Chen, Wenqing Xu, Zhizhi Wang, Kaijie He
Journal: Cell Reports Medicine (2022)
<scp>Neutrophil‐Erythrocyte</scp> Rosettes in <scp>COVID</scp>‐19
Authors: Bingwen Eugene Fan, Jia Qi Wendy Leong, Bernard Pui Lam Leung, Weng Yik Ng, Wendy Siew Lian Lim, Wei Yong Kevin Wong, Wei Yin Lim, Siew Ping Connie Chen, Sheem Ying Rachel Yap, Guat Bee Tan, Minyang Chow, Sharavan Sadasiv Mucheli, Ponnudurai Kuperan, Christian Aledia Gallardo
Journal: American Journal of Hematology (2022)

The authors declare that they have no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational study
Authors: Rudzani C Mashau, Susan T Meiring, Vanessa C Quan, Jeremy Nel, Greg S Greene, Andrea Garcia, Colin Menezes, Denasha L Reddy, Michelle Venter, Sarah Stacey, Matamela Madua, Lia Boretti, Thomas S Harrison, Graeme Meintjes, Amir Shroufi, Laura Trivino-Duran, John Black, Nelesh P Govender, Shareef Abrahams, Vanessa Pearce, Masego Moncho, Jeanette Wadula, Motlatji Maloba, Anwar Hoosen, Charl Verwey, Colin Menezes, David Moore, Dina Pombo, Gary Reubenson, Grace Ntlemo, Lauren Richards, Maphoshane Nchabeleng, Merika Tsitsi, Moamokgethi Moshe, Mohammed Said, Molebogeng Kolojane, Lesego Mothibi, Nicolette Du Plessis, Rispah Chomba, Teena Thomas, Theunis Avenant, Trusha Nana, Vindana Chibabhai, Adhil Maharj, Douglas Wilson, Fathima Naby, Halima Dawood, Khine Swe Swe Han, Lisha Sookan, Nomonde Dlamini, Praksha Ramajathan, Prasha Mahabeer, Prathna Bhola, Romola Naidoo, Sumayya Haffejee, Surendra Sirkar, Yeishna Ramkillawan, Ken Hamese, Ngoaka Sibiya, Phetho Mangena, Ruth Lekalakala, Greta Hoyland, Sindi Ntuli, Ebrahim Variava, Ignatius Khantsi, Omphile Mekgoe, Adrian Brink, Elizabeth Prentice, Kessendri Reddy, Andrew Whitelaw, Ebrahim Hoosien, Inge Zietsman, Terry Marshall, Xoliswa Poswa, Chetna Govind, Juanita Smit, Keshree Pillay, Sharona Seetharam, Victoria Howell, Catherine Samuel, Marthinus Senekal, Colleen Bamford, Andries Dreyer, Louis Marcus, Warren Lowman, Anne von Gottberg, Anthony Smith, Azwifarwi Mathunjwa, Cecilia d'Abreu, Cecilia Miller, Cheryl Cohen, Farzana Ismail, Harry Moultrie, Husna Ismail, Jacqueline Weyer, Jackie Kleynhans, Jenny Rossouw, John Frean, Joy Ebonwu, Judith Mwansa-Kambafwile, Juno Thomas, Kate Bishop, Kerrigan McCarthy, Liliwe Shuping, Linda de Gouveia, Linda Erasmus, Adrian Puren, Lucille Blumberg, Marshagne Smith, Martha Makgoba, Michelle Groome, Mignon du Plessis, Mimmy Ngomane, Mokupi Manaka, Myra Moremi, Nazir Ismail, Neo Legare, Nicola Page, Nombulelo Hoho, Olga Perovic, Phuti Sekwadi, Rindidzani Magobo, Ruth Mpembe, Sibongile Walaza, Siyanda Dlamini, Sunnieboy Njikho, Tiisetso Lebaka, Wendy Ngubane
Journal: The Lancet Infectious Diseases (2022)
The Principle of Autonomy in Biomedical- and Neuroethics
Authors: Barend W. Florijn
Journal: The American Journal of Bioethics (2022)

This article refers to:Meaningful Respect for the Autonomy of Persons with “Completed Life”: An Analysis in Light of Empirical ResearchThe Role of Suffering in the “Tired of Life” DebateSuffering and the Completed LifeThe Unstable Boundary of Suffering-Based Euthanasia Regimes
Authors’ Reply: Clinical Studies of Vaccine Efficacy
Authors: Samira Bell, Jacqueline Campbell, Emilie Lambourg, Patrick Mark
Journal: Journal of the American Society of Nephrology (2022)

We thank Ashby for his interest in our study. Our data clearly demonstrate a two-dose coronavirus disease 2019 (COVID-19) vaccination regimen is insufficient protection for patients either on dialysis or with a kidney transplant. This finding is entirely in keeping with other emergent data
Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta‐analysis
Authors: Alexios S. Antonopoulos, Ioannis Panagiotopoulos, Alexandrina Kouroutzoglou, Georgios Koutsis, Pantelis Toskas, Georgios Lazaros, Konstantinos Toutouzas, Dimitris Tousoulis, Konstantinos Tsioufis, Charalambos Vlachopoulos
Journal: European Journal of Heart Failure (2022)
European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials
Authors: Anne B. Chang, Angela Zacharasiewicz, Vikas Goyal, Jeanette Boyd, Efthymia Alexopoulou, Stefano Aliberti, Leanne Bell, Andrew Bush, Alison Claydon, Carolina Constant, Rebecca Fortescue, Adam T. Hill, Bulent Karadag, Zena Powell, Christine Wilson, Keith Grimwood, Ahmad Kantar, James Chalmers, Andrew Collaro, Kostas Douros, Matthias Griese, Jonathan Grigg, Andreas Hector, Oleksandr Mazulov, Fabio Midulla, Alexander Möller, Marijke Proesmans, Stephanie Yerkovich
Journal: European Respiratory Journal (2022)

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6–7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.